PCL/ASA药物控释系统结构拓扑优化及瞬态释药性能  

Structural topology optimization and transient drug release performance of PCL/ASA controlled drug delivery system

作　　者：高扬 孟繁舒 闵浩楠 剌焕军 陈磊[1] 后振中[3] GAO Yang;MENG Fanshu;MIN Haonan;LA Huanjun;CHEN lei;HOU Zhenzhong(College of Mechanical Engineering,Xi'an University of Science and Technology,Xi'an 710054,China;State Key Laboratory for Manufacturing Systems Engineering,Xi'an Jiaotong University,Xi'an 710049,China;College of Materials Science and Engineering,Xi'an University of Science and Technology,Xi'an 710054,China)

机构地区：[1]西安科技大学机械工程学院,西安710054 [2]西安交通大学机械制造系统工程国家重点实验室,西安710049 [3]西安科技大学材料科学与工程学院,西安710054

出　　处：《工程塑料应用》2024年第2期87-93,共7页Engineering Plastics Application

基　　金：陕西省重点研发计划项目(2023-YBGY-448);西安交通大学机械制造系统工程国家重点实验室开放基金项目(sklms2022019);国家自然科学基金青年基金项目(51605379);陕西省教育厅服务地方专项计划项目(22JC052)。

摘　　要：以聚己内酯(PCL)为载体材料,阿司匹林(ASA)为待释放药物,提出一种PCL/ASA药物控释系统,以实现医工结合背景下药物控释系统的个性化定制及释药量的参数化调节。首先,基于菲克扩散定律建立了PCL/ASA药物控释系统的释药模型,以设计域平均浓度与目标浓度之差的最小值作为优化目标,采用拓扑优化方法对PCL/ASA药物控释系统的结构进行拓扑优化设计。其次,对所获得的拓扑优化结构进行几何重构,得到清晰的流道结构,并研究了不同药物储库形状和流道结构对瞬态释药性能的影响。最后,制备PCL/ASA药物控释系统并进行体外药物释放实验,验证了优化方法和模型的合理性。结果表明,几何重构方法可以很好地保留拓扑优化的流道结构,具备较高的可靠性。拓扑优化方法所获得的流道结构展现出较好的药物控释性能,药物释放趋势趋于零级释放。基于拓扑优化设计的PCL/ASA药物控释系统可以在35.03~43.86 mol/m3范围内实现ASA浓度的参数化调节,呈现出较好的释药量调节能力。该研究为医工结合背景下优化药物控释系统结构、实现按需给药提供了一种新的手段。Taking polycaprolactone(PCL)as the carrier material and aspirin(ASA)as the drug to be released,a PCL/ASA controlled drug delivery system was proposed,so as to enable the personalized customization of controlled drug delivery systems and the parametric adjustment of drug release in the context of the combination medicine and industry.Firstly,a drug release model for PCL/ASA controlled drug delivery system was developed based on Fick's diffusion law.The minimum of the difference between the average concentration of the design domain and the target concentration was used as the optimization objective,and topology optimization was used to optimize the structure of the controlled drug delivery system.Secondly,a geometric reconstruction of the topologically optimized structure was performed to obtain a clear flow channel structure,and the effects of different drug reservoir shapes and flow channel structures on the transient drug release performance were investigated.Finally,a PCL/ASA controlled drug delivery system was prepared and the in vitro release experiments were performed to validate the rationality of the optimization method and model.The results show that the geometric reconstruction can well preserve the flow channel structure optimized by the topology with high reliability.The flow channel structure obtained by the topology optimization method exhibits better drugcontrolled release performance,with a tendency towards zero-order release.The PCL/ASA controlled drug delivery system based on topology optimization can achieve parametric adjustment of ASA concentration in the range of 35.03 mol/m3 to 43.86 mol/m3,showing a good ability to adjust drug release.This study provides a new method to optimize the structure of controlled drug delivery systems and enable on-demand drug delivery in the context of a medical-industrial combination.

关 键 词：聚己内酯 拓扑优化 药物控释系统 几何重构 释药性能 

分 类 号：TB324[一般工业技术—材料科学与工程]